CDK4/6 Inhibition and Surgery Endeavors Help Break Ground for Innovative Breast Cancer Treatments

Clinical trials and individualized therapies are paving the way for advances in the treatment of patients with HER2-positive, estrogen receptor (ER)­–positive, and triple-negative breast cancer, Adam M. Brufsky, MD, PhD, explained.

The 2022 ASCO Annual Meeting will provide further opportunities to exchange updates in the breast cancer space, Brufsky added.

“We have better options now for triple-negative breast cancer, HER2-positive breast cancer, and ER-positive breast cancer. [With the innovations surrounding CDK4/6 inhibitors and other treatments], where we go next in this space is important for patient care,” Brufsky said in an interview with OncLive^® following an Institutional Perspectives in Cancer (IPC) webinar, which he chaired.

In the interview, Brufsky, a professor of medicine at the University of Pittsburgh School of Medicine, the associate division chief for the Division of Hematology/Oncology at the University of Pittsburgh School of Medicine’s Department of Medicine, the medical director of the Magee-Women’s Cancer Program, at the University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, reviewed key points from each presentation from the meeting. Brufsky emphasized the importance of tyrosine kinase inhibitors (TKIs) in HER2-postive breast cancer and highlighted the potential benefits of local salvage radiation therapy in patients with oligometastatic or de novo stage IV breast cancer.

Brufksy is also the codirector of the Comprehensive Breast Cancer Center, and the associate director for clinical investigations.

OncLive^®: Could you provide a brief overview of your presentation on hormone receptor (HR)–positive, HER2-positive, and triple-negative breast cancer?

Brufsky: [This IPC event was looking ahead to ASCO and was an opportunity for us to share] where we are in breast cancer. I talked about HER2-positive breast cancer, as well as some advances with CDK4/6 inhibitors.

[Some of the trials I discussed included [the phase 3 EMBRACA trial (NCT01945775)], as well as [the phase 3 KEYNOTE-355 trial (NCT02819518) in triple-negative breast cancer]. I also talked about the [phase 3] OlympiAD trial [NCT02000622], which investigated PARP inhibitors. In terms of the metastatic trials, I compared the overall survival [OS] data that have come out regarding CDK4/6 inhibitors from the [phase 3 PALOMA-2 trial (NCT01740427) vs the phase 3 PALOMA-3 trial (NCT01942135) and the phase 3 MONALEESA-2 trial (NCT01958021) vs the phase 3 MONALEESA-3 trial (NCT02422615)]. I also gave a preview of some of the topics that will be presented at ASCO, such as the [phase 3 DESTINY-Breast04 trial [NCT03734029].

Priya Rastogi, MD, of UPMC Hillman Cancer Center, also presented on HER2-positive breast cancers. What interesting information came out of this presentation?

Dr Rastogi talked about [the phase 3 KATHERINE trial (NCT01772472)], regarding the HER2-positive population. She also summarized where we are with [the phase 3] DESTINY-Breast03 trial [NCT03529110]. [A large portion of her presentation focused on] where we are with HER2 TKIs such as tucatinib [(Tukysa), as well as monoclonal antibodies such as pertuzumab (Perjeta) and trastuzumab (Herceptin)].

Parul Barry, MD, of UPMC Hillman Cancer Center, spoke on radiation therapy. What were you excited to hear about from this presentation?

Dr Barry talked about some updates in radiation therapy and touched on predictors of benefit with [local salvage] radiation therapy. She also previewed findings from the [phase 2/3] BR002 trial [NCT02364557] that will be presented at ASCO. This trial investigated [salvage radiation vs systemic therapy] in women with oligometastatic disease to see if either approach improves survival. It’s an important trial to talk about.

What interested you about the presentation given by Priscilla McAuliffe, MD, PhD, of UPMC Hillman Cancer Center, which focused on surgical updates in this space?

[One of the big questions now is: How do we treat patients] with de novo stage IV disease? Do we do surgery? Dr McAuliffe discussed where we are with that. [She talked about] a presentation given at the [2020 ASCO Annual Meeting that revealed biases in the results of several retrospective trials that seemed to favor surgery in this population].

Additionally, she gave some updated data regarding the ESMO [guidelines, which recommend locoregional therapy of the primary tumor in younger patients with local symptoms but not in patients with asymptomatic local disease]. She talked about what that decision means and [the direction] we’re going in [regarding the role of local therapy in stage IV metastatic breast cancer].

What are you looking forward to from the 2022 ASCO Annual Meeting?

Expanding the universe of antibody-drug conjugates is going to be a big topic. I’m also interested to see some survival data from some of the big CDK4/6 inhibitor trials. Those are probably going to be the big news items in breast cancer.

Based on all the presentations we talked about, what is the main message you would like to give to colleagues?

There has been much innovation in breast cancer. We’re moving toward an era, at least in HER2-positive and ER­-positive disease, where we’re controlling disease for quite a long time. [Now that this is happening, we’ll start facing new sets of questions], like determining what to do when patients have been on therapy for several years. The triple-negative breast cancer space has been advancing as well.

As the chair of this IPC meeting, what would you say is the importance of meetings like these for oncologists?

These meetings are important because we often can’t go to meetings in person, especially with the pandemic. [Virtual meetings allow us to more easily] carve out time. Meetings like this also help busy clinicians get a good sense of what the current state of the art is in a particular tumor type, in this case, breast cancer.